Is SRC p.Phe175= (c.525C>T) pathogenic?

SRC p.Phe175= (c.525C>T) is classified Likely benign in SRC (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-12-03). Ultra-rare (popmax 0.011%, sas); Associated with SRC-related disorder.

What condition is associated with SRC p.Phe175= (c.525C>T)?

SRC p.Phe175= (c.525C>T) is associated with SRC-related disorder (ClinVar).

How common is SRC p.Phe175= (c.525C>T) in the general population?

SRC p.Phe175= (c.525C>T) is ultra-rare (popmax 0.011%, sas) (gnomAD).

SRC p.Phe175=

c.525C>T · rs559060103 · VCV3033317

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.011%, sas)

Conditions

SRC-related disorder

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 2.2	GERP 2.1, phastCons 1
Overall
CADD	12.81	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.011% South Asian · 10/91,080 alleles

Filtering AF 0.00594% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00453%

Overall 0.000743% 12/1,614,046 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.011%	9,108
Remaining individualsnot grpmax-eligible	0.0032%	31,254

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.Phe175=
Coding: c.525C>T
MANE Select: NM_198291
dbSNP: rs559060103
Type: single nucleotide variant
Location: chr20:37394249 (GRCh38)
Gene constraint: LOEUF 0.383 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.59 · 79 PDB
Residue 175: the sh2 domain; a β-strand

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

Disease context

SRC-related disorder

Similar variants

SRC p.Glu527Lys Pathogenic/Likely pathogenic ★★ same condition
SRC c.450-8A>T Likely benign same condition
SRC p.Glu283= Likely benign same condition
SRC p.Pro532= Likely benign same condition
SRC p.Ser212= Likely benign same condition
SRC p.Glu492Lys Uncertain significance ★★ ⚠ same type
SRC c.1117-180C>T Benign ★★ same type
SRC c.1117-9C>T Likely 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-phe175 (accessed [today's date]).

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