Is SRC p.Arg271Trp (c.811C>T) pathogenic?

SRC p.Arg271Trp (c.811C>T) is classified Uncertain significance in SRC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-27). AlphaMissense: likely benign (0.2731); Ultra-rare (popmax 0.039%, mid).

How common is SRC p.Arg271Trp (c.811C>T) in the general population?

SRC p.Arg271Trp (c.811C>T) is ultra-rare (popmax 0.039%, mid) (gnomAD).

What do computational predictors say about SRC p.Arg271Trp (c.811C>T)?

AlphaMissense predicts likely benign (score 0.2731) — an in-silico prediction, not a clinical call.

SRC p.Arg271Trp

c.811C>T · rs148049198 · VCV2310404

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2731 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.039%, mid)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2731	likely benign
REVEL	0.678	pathogenic-leaning
SaProt	LLR -12.93	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP -0.24, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 3,892 bp · p 4.5e-05 · regional, not allelic
Overall
CADD	27.9	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 0.039% Middle Eastern · 2/5,124 alleles

Filtering AF 0.0193% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0184%

Overall 0.0177% 285/1,611,958 alleles · ultra-rare exomes 254/1,459,616 · genomes 31/152,342 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.039%	2,562
European (non-Finnish)	0.0215%	4,645
Remaining individualsnot grpmax-eligible	0.016%	6,237
African / African-American	0.012%	8,335
East Asian	0.00669%	14,952
Admixed American	0.00667%	14,994
South Asian	0.0022%	45,434
Finnishnot grpmax-eligible	0.00157%	63,536

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.Arg271Trp
Coding: c.811C>T
MANE Select: NM_198291
dbSNP: rs148049198
Type: single nucleotide variant
Location: chr20:37397806 (GRCh38)
Gene constraint: LOEUF 0.383 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.59 · 79 PDB
Residue 271: 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.1117-180C>T Benign ★★ same type
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-arg271trp (accessed [today's date]).

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