Is SRC p.Val340Ile (c.1018G>A) pathogenic?

SRC p.Val340Ile (c.1018G>A) is classified Uncertain significance in SRC (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-06). AlphaMissense: likely benign (0.1306); Very rare (popmax 0.00401%, afr).

How common is SRC p.Val340Ile (c.1018G>A) in the general population?

SRC p.Val340Ile (c.1018G>A) is very rare (popmax 0.00401%, afr) (gnomAD).

What do computational predictors say about SRC p.Val340Ile (c.1018G>A)?

AlphaMissense predicts likely benign (score 0.1306) — an in-silico prediction, not a clinical call.

SRC p.Val340Ile

c.1018G>A · rs867593338 · VCV2234627

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1306 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1306	likely benign
REVEL	0.512	indeterminate
SaProt	LLR -8.52	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.47	unconstrained · MANE · 5,565 bp · p 1.1e-23 · regional, not allelic
Overall
CADD	27.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.00401% African / African-American · 3/74,898 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000682% 11/1,613,054 alleles · very rare exomes 6/1,460,878 · genomes 5/152,176 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,966
East Asian	0.00223%	44,852
South Asian	0.0011%	90,924
European (non-Finnish)	0.000509%	196,577

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: SRC
Protein: p.Val340Ile
Coding: c.1018G>A
MANE Select: NM_198291
dbSNP: rs867593338
Type: single nucleotide variant
Location: chr20:37400273 (GRCh38)
Gene constraint: LOEUF 0.383 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.59 · 79 PDB
Residue 340: the protein kinase domain; a β-strand

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

Similar variants

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SRC c.1117-9C>T Likely benign ★★ same type
SRC c.1271-55= Benign ★★ same type
SRC c.449+9C>T Benign/Likely benign ★★ same type
SRC c.553+8C>T Benign/Likely benign ★★ same type
SRC c.554-5C>T Benign ★★ 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/src-p-val340ile (accessed [today's date]).

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