Is SRC p.Arg480Gln (c.1439G>A) pathogenic?

SRC p.Arg480Gln (c.1439G>A) is classified Uncertain significance in SRC (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-17). AlphaMissense: likely benign (0.2746); Very rare (popmax 0.00135%, afr).

How common is SRC p.Arg480Gln (c.1439G>A) in the general population?

SRC p.Arg480Gln (c.1439G>A) is very rare (popmax 0.00135%, afr) (gnomAD).

What do computational predictors say about SRC p.Arg480Gln (c.1439G>A)?

AlphaMissense predicts likely benign (score 0.2746) — an in-silico prediction, not a clinical call.

SRC p.Arg480Gln

c.1439G>A · rs1173914321 · VCV2548214

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2746 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00135%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2746	likely benign
REVEL	0.435	indeterminate
SaProt	LLR -7.35	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	31.0	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 0.00135% African / African-American · 1/73,988 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000212% 3/1,412,992 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00135%	73,988
European (non-Finnish)	0.000173%	579,451

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.Arg480Gln
Coding: c.1439G>A
MANE Select: NM_198291
dbSNP: rs1173914321
Type: single nucleotide variant
Location: chr20:37403207 (GRCh38)
Gene constraint: LOEUF 0.383 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.59 · 79 PDB
Residue 480: the protein kinase domain

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

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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-arg480gln (accessed [today's date]).

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