Is SRC p.Gly282= (c.846C>T) pathogenic?

SRC p.Gly282= (c.846C>T) is classified Conflicting classifications of pathogenicity in SRC (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-05-19). Ultra-rare (popmax 0.0568%, amr).

How common is SRC p.Gly282= (c.846C>T) in the general population?

SRC p.Gly282= (c.846C>T) is ultra-rare (popmax 0.0568%, amr) (gnomAD).

SRC p.Gly282=

c.846C>T · rs367543242 · VCV98528

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0568%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.76	donor gain · deltas
Pangolin	Δ0.26	gain · loss 0.06 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 1.1	GERP -4.2, phastCons 1
Overall
CADD	20.9	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0568% Admixed American · 34/59,842 alleles

Filtering AF 0.0417% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0366%

Overall 0.00664% 107/1,610,314 alleles · ultra-rare exomes 82/1,458,122 · genomes 25/152,192 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0568%	1,760
Remaining individualsnot grpmax-eligible	0.0145%	6,914
European (non-Finnish)	0.005%	19,991
South Asian	0.00331%	30,232
African / African-American	0.00267%	37,428

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.Gly282=
Coding: c.846C>T
MANE Select: NM_198291
dbSNP: rs367543242
Type: single nucleotide variant
Location: chr20:37397841 (GRCh38)
Gene constraint: LOEUF 0.383 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.59 · 79 PDB
Residue 282: the protein kinase domain; a β-strand; a binding site

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-gly282 (accessed [today's date]).

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