Is EMC10 p.Arg71Trp (c.211C>T) pathogenic?

EMC10 p.Arg71Trp (c.211C>T) is classified Uncertain significance in EMC10 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-16). AlphaMissense: likely pathogenic (0.88); Very rare (popmax 0.00712%, nfe); Associated with Inborn genetic diseases.

What condition is associated with EMC10 p.Arg71Trp (c.211C>T)?

EMC10 p.Arg71Trp (c.211C>T) is associated with Inborn genetic diseases (ClinVar).

How common is EMC10 p.Arg71Trp (c.211C>T) in the general population?

EMC10 p.Arg71Trp (c.211C>T) is very rare (popmax 0.00712%, nfe) (gnomAD).

What do computational predictors say about EMC10 p.Arg71Trp (c.211C>T)?

AlphaMissense predicts likely pathogenic (score 0.88) — an in-silico prediction, not a clinical call.

EMC10 p.Arg71Trp

c.211C>T · rs148764183 · VCV2519955

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.88 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00712%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.88	likely pathogenic
REVEL	0.487	indeterminate
SaProt	LLR -12.57	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 0.98, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 5,711 bp · p 0.019 · regional, not allelic
Overall
CADD	29.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00712% European (non-Finnish) · 84/1,179,026 alleles

Filtering AF 0.00588% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00541%

Overall 0.00652% 105/1,610,296 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0161%	6,228
European (non-Finnish)grpmax	0.00712%	14,036
Finnishnot grpmax-eligible	0.0047%	21,272
Ashkenazi Jewishnot grpmax-eligible	0.00339%	29,534
Admixed American	0.00335%	29,894
South Asian	0.00332%	30,121
East Asian	0.00223%	44,808
African / African-American	0.00134%	74,814

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: EMC10
Protein: p.Arg71Trp
Coding: c.211C>T
MANE Select: NM_206538
dbSNP: rs148764183
Type: single nucleotide variant
Location: chr19:50478980 (GRCh38)
Gene constraint: LOEUF 1.606 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.60 · 10 PDB
Residue 71: a β-strand

Full EMC10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EMC10 p.Arg97Ter Pathogenic ★★ same condition
EMC10 p.Ala134Val Uncertain significance ★★ ⚠ same condition
EMC10 p.Arg88Gln Uncertain significance ★★ ⚠ same condition
EMC10 p.Ser143Trp Uncertain significance ★★ ⚠ same condition
EMC10 p.Tyr127Cys Uncertain significance ★★ ⚠ same condition
EMC10 c.679-224C>T Uncertain significance ★ same condition
EMC10 p.Ala103Thr Uncertain significance ★ ⚠ same condition
EMC10 p.Ala224Thr Uncertain significance ★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/emc10-p-arg71trp (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown