Is EGFR p.Ala13Val (c.38C>T) pathogenic?

EGFR p.Ala13Val (c.38C>T) is classified Conflicting classifications of pathogenicity in EGFR (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-24). AlphaMissense: likely benign (0.0917); Ultra-rare (popmax 0.0609%, amr); Associated with hereditary neoplastic syndrome.

What condition is associated with EGFR p.Ala13Val (c.38C>T)?

EGFR p.Ala13Val (c.38C>T) is associated with hereditary neoplastic syndrome, lung cancer, inflammatory skin and bowel disease, neonatal, 2 (ClinVar).

How common is EGFR p.Ala13Val (c.38C>T) in the general population?

EGFR p.Ala13Val (c.38C>T) is ultra-rare (popmax 0.0609%, amr) (gnomAD).

What do computational predictors say about EGFR p.Ala13Val (c.38C>T)?

AlphaMissense predicts likely benign (score 0.0917) — an in-silico prediction, not a clinical call.

EGFR p.Ala13Val

c.38C>T · rs567894670 · VCV858191

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0917 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0609%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.0917	likely benign
REVEL	0.185	benign-leaning
SaProt	LLR -5.92	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 -1.4	GERP -2.5
Regional constraint	o/e 1.72	unconstrained · MANE · 84 bp · p 9.2e-06 · regional, not allelic
Overall
CADD	0.285	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 0.0609% Admixed American · 32/52,524 alleles

Filtering AF 0.0443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0386%

Overall 0.00269% 41/1,522,070 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0609%	1,641
Remaining individualsnot grpmax-eligible	0.00349%	28,666
African / African-American	0.00287%	34,832
South Asian	0.00119%	84,078
European (non-Finnish)	0.000354%	282,749

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: EGFR
Protein: p.Ala13Val
Coding: c.38C>T
MANE Select: NM_005228
dbSNP: rs567894670
Type: single nucleotide variant
Location: chr7:55019315 (GRCh38)
Gene constraint: LOEUF 0.475 · pLI 0.98 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 76.29 · 393 PDB

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

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: lung cancer inflammatory skin and bowel disease, neonatal, 2

Similar variants

EGFR p.Ala13Glu Uncertain significance ★★ ⚠ same residue
EGFR p.Ala13= Likely benign ★★ same residue
EGFR p.Ala13Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
EGFR p.Ala13Ser Uncertain significance ★ ⚠ same residue
EGFR p.Gly428Asp Pathogenic ★★ same condition
EGFR c.1207+5G>A Uncertain significance ★★ same condition
EGFR c.1298+3A>G Uncertain significance ★★ same condition
EGFR c.1298+4A>G 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/egfr-p-ala13val (accessed [today's date]).

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