Is ERMAP p.Ala4Val (c.11C>T) pathogenic?

ERMAP p.Ala4Val (c.11C>T) is classified Benign in ERMAP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2018-02-25). AlphaMissense: likely benign (0.2564); Common (popmax 5.61%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about ERMAP p.Ala4Val (c.11C>T)?

AlphaMissense predicts likely benign (score 0.2564) — an in-silico prediction, not a clinical call.

ERMAP p.Ala4Val

Q: How common is ERMAP p.Ala4Val (c.11C>T) in the general population?

ERMAP p.Ala4Val (c.11C>T) is common (popmax 5.61%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.11C>T · rs35757049 · VCV775539

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2564 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 5.61%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2564	likely benign
REVEL	0.04	moderately benign-leaning
SaProt	LLR -6.84	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP 0.67, phastCons 0.98
Regional constraint	o/e 0.93	unconstrained · MANE · 13 kb · p 0.085 · regional, not allelic
Overall
CADD	20.8	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 5.61% African / African-American · 4,206/74,986 alleles

Filtering AF 5.47% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.41%

Overall 0.312% 5,041/1,614,044 alleles · common exomes 2,650/1,461,836 · genomes 2,391/152,208 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.61%	18
Admixed American	0.437%	229
Remaining individualsnot grpmax-eligible	0.402%	249
Middle Eastern	0.396%	253
European (non-Finnish)	0.0236%	4,245
Finnishnot grpmax-eligible	0.0156%	6,403
South Asian	0.011%	9,107

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: ERMAP
Protein: p.Ala4Val
Coding: c.11C>T
MANE Select: NM_001017922
dbSNP: rs35757049
Type: single nucleotide variant
Location: chr1:42830459 (GRCh38)
Gene constraint: LOEUF 0.913 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.22
Residue 4: a UniProt-annotated variant site (in)

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

Similar variants

ERMAP p.Arg73= Benign ★★ same type
ERMAP p.Ala157Ser Uncertain significance ★ ⚠ same type
ERMAP p.Ala34Ser Uncertain significance ★ ⚠ same type
ERMAP p.Ala449Ser Uncertain significance ★ ⚠ same type
ERMAP p.Arg117His Uncertain significance ★ ⚠ same type
ERMAP p.Arg231Gly Uncertain significance ★ ⚠ same type
ERMAP p.Arg234Gln Uncertain significance ★ ⚠ same type
ERMAP p.Arg234Trp 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/ermap-p-ala4val (accessed [today's date]).

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