Is SRC p.Thr129= (c.387A>G) pathogenic?

SRC p.Thr129= (c.387A>G) is classified Benign/Likely benign in SRC (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-04-23). Rare (popmax 0.638%, afr).

How common is SRC p.Thr129= (c.387A>G) in the general population?

SRC p.Thr129= (c.387A>G) is rare (popmax 0.638%, afr) (gnomAD).

SRC p.Thr129=

c.387A>G · rs149325729 · VCV714899

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.638%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -8.2	GERP -4.2
Overall
CADD	0.417	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.638% African / African-American · 479/75,054 alleles

Filtering AF 0.591% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.572%

Overall 0.0341% 551/1,614,092 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.638%	157
Middle Eastern	0.066%	1,516
Admixed American	0.0533%	1,876
Remaining individualsnot grpmax-eligible	0.048%	2,083
South Asian	0.0022%	45,539
European (non-Finnish)	0.000339%	295,005

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.Thr129=
Coding: c.387A>G
MANE Select: NM_198291
dbSNP: rs149325729
Type: single nucleotide variant
Location: chr20:37393931 (GRCh38)
Gene constraint: LOEUF 0.383 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.59 · 79 PDB
Residue 129: the sh3 domain; a turn

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

Similar variants

SRC p.Glu527Lys Pathogenic/Likely pathogenic ★★ same type
SRC p.Glu492Lys Uncertain significance ★★ ⚠ same type
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-thr129 (accessed [today's date]).

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