Is SRC c.250+211A>G pathogenic?

SRC c.250+211A>G is classified Benign in SRC (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-19). Common (popmax 100%, mid) — too common for a highly-penetrant pathogenic allele.

SRC c.250+211A>G

Q: How common is SRC c.250+211A>G in the general population?

SRC c.250+211A>G is common (popmax 100%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs4809610 · VCV1239174

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 100%, mid) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +211	deep intronic (+211 nt into the intron)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.031	GERP -2.5
Non-coding constraint	Z 6.70	1 kb window · o/e 0.50 · regional · uncalibrated
Overall
CADD	7.682	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 100% Middle Eastern · 288/288 alleles

Filtering AF 99.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 99.1%

Overall 100% 151,663/151,696 alleles · common

Ancestry group	Frequency	1 in
East Asian	100%	1
South Asian	100%	1
Ashkenazi Jewishnot grpmax-eligible	100%	1
Amishnot grpmax-eligible	100%	1
Middle Easterngrpmax	100%	1
Remaining individualsnot grpmax-eligible	100%	1
European (non-Finnish)	100%	1
Finnishnot grpmax-eligible	100%	1
Admixed American	100%	1
African / African-American	99.9%	1

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
Coding: c.250+211A>G
MANE Select: NM_198291
dbSNP: rs4809610
Type: single nucleotide variant
Location: chr20:37384614 (GRCh38)
Gene constraint: LOEUF 0.383 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.59 · 79 PDB

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-c-250-plus-211a-g (accessed [today's date]).

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