Is EMC10 p.Ser136Phe (c.407C>T) pathogenic?

EMC10 p.Ser136Phe (c.407C>T) is classified Uncertain significance in EMC10 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-25). AlphaMissense: likely pathogenic (0.5934); Very rare (popmax 0.000783%, nfe); Associated with Inborn genetic diseases.

What condition is associated with EMC10 p.Ser136Phe (c.407C>T)?

EMC10 p.Ser136Phe (c.407C>T) is associated with Inborn genetic diseases (ClinVar).

How common is EMC10 p.Ser136Phe (c.407C>T) in the general population?

EMC10 p.Ser136Phe (c.407C>T) is very rare (popmax 0.000783%, nfe) (gnomAD).

What do computational predictors say about EMC10 p.Ser136Phe (c.407C>T)?

AlphaMissense predicts likely pathogenic (score 0.5934) — an in-silico prediction, not a clinical call.

EMC10 p.Ser136Phe

c.407C>T · VCV3844592

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5934 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000783%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5934	likely pathogenic
REVEL	0.273	benign-leaning
SaProt	LLR -8.19	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 1.5, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 5,711 bp · p 0.019 · regional, not allelic
Overall
CADD	27.6	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000783% European (non-Finnish) · 9/1,149,072 alleles

Filtering AF 0.000369% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000267%

Overall 0.000579% 9/1,554,412 alleles · very rare

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.Ser136Phe
Coding: c.407C>T
MANE Select: NM_206538
Type: single nucleotide variant
Location: chr19:50480585 (GRCh38)
Gene constraint: LOEUF 1.606 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.60 · 10 PDB
Residue 136: an α-helix

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-ser136phe (accessed [today's date]).

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