Is EMC7 p.Phe77Val (c.229T>G) pathogenic?

EMC7 p.Phe77Val (c.229T>G) is classified Uncertain significance in EMC7 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-03-19). AlphaMissense: likely pathogenic (0.9384); Low-frequency (popmax 2.81%, nfe).

How common is EMC7 p.Phe77Val (c.229T>G) in the general population?

EMC7 p.Phe77Val (c.229T>G) is low-frequency (popmax 2.81%, nfe) (gnomAD).

What do computational predictors say about EMC7 p.Phe77Val (c.229T>G)?

AlphaMissense predicts likely pathogenic (score 0.9384) — an in-silico prediction, not a clinical call.

EMC7 p.Phe77Val

c.229T>G · rs1901174527 · VCV2278388

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9384 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.81%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9384	likely pathogenic
REVEL	0.804	moderately pathogenic-leaning
SaProt	LLR -10.28	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.71 · evaluated, not missing
Constraint at this position
Conservation	phyloP 9.2	GERP 1.8, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 11 kb · p 0.11 · regional, not allelic
Overall
CADD	31.0	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 2.81% European (non-Finnish) · 32,550/1,156,558 alleles

Filtering AF 2.79% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.78%

Overall 2.39% 37,939/1,586,290 alleles · low-frequency

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	2.81%	36
Remaining individualsnot grpmax-eligible	2.42%	41
East Asian	2.03%	49
Ashkenazi Jewishnot grpmax-eligible	1.57%	64
Middle Eastern	1.34%	75
Finnishnot grpmax-eligible	1.19%	84
African / African-American	1.05%	95
South Asian	0.735%	136
Admixed American	0.437%	229

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: EMC7
Protein: p.Phe77Val
Coding: c.229T>G
MANE Select: NM_020154
dbSNP: rs1901174527
Type: single nucleotide variant
Location: chr15:34101611 (GRCh38)
Gene constraint: LOEUF 0.375 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.54 · 14 PDB
Residue 77: a β-strand

Full EMC7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EMC7 p.Gly38= Benign ★★ same type
EMC7 p.Ala238Pro Uncertain significance ★ ⚠ same type
EMC7 p.Ala30Val Uncertain significance ★ ⚠ same type
EMC7 p.Ala31Thr Uncertain significance ★ ⚠ same type
EMC7 p.Ala4Val Uncertain significance ★ ⚠ same type
EMC7 p.Arg44His Uncertain significance ★ ⚠ same type
EMC7 p.Asp43Asn Uncertain significance ★ ⚠ same type
EMC7 p.Asp43His Uncertain significance ★ ⚠ same type

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/emc7-p-phe77val (accessed [today's date]).

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