Is SRR p.Val174Phe (c.520G>T) pathogenic?

SRR p.Val174Phe (c.520G>T) is classified Uncertain significance in SRR (ClinVar, Single submitter, 2 submitters; last evaluated 2024-09-10). AlphaMissense: likely benign (0.2503); Ultra-rare (popmax 0.0165%, mid).

How common is SRR p.Val174Phe (c.520G>T) in the general population?

SRR p.Val174Phe (c.520G>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about SRR p.Val174Phe (c.520G>T)?

AlphaMissense predicts likely benign (score 0.2503) — an in-silico prediction, not a clinical call.

SRR p.Val174Phe

c.520G>T · VCV3449491

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2503 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2503	likely benign
REVEL	0.756	pathogenic-leaning
SaProt	LLR -10.33	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	Δ0.47	acceptor loss at this position · masked 0 · deltas
Pangolin	Δ0.49	loss · gain 0.08 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 5.8	GERP -0.13, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 8,309 bp · p 0.12 · regional, not allelic
Overall
CADD	23.2	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 0.0165% Middle Eastern · 1/6,060 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.00378% 61/1,613,932 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,060
Admixed American	0.01%	9,998
South Asian	0.00439%	22,769
European (non-Finnish)	0.0039%	25,652
African / African-American	0.00267%	37,452
East Asian	0.00223%	44,896
Remaining individualsnot grpmax-eligible	0.0016%	62,484

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: SRR
Protein: p.Val174Phe
Coding: c.520G>T
MANE Select: NM_021947
Type: single nucleotide variant
Location: chr17:2321542 (GRCh38)
Gene constraint: LOEUF 0.864 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.95 · 11 PDB

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

Similar variants

SRR p.Ala167Thr Uncertain significance ★ ⚠ same type
SRR p.Arg58His Uncertain significance ★ ⚠ same type
SRR p.Arg58Pro Uncertain significance ★ ⚠ same type
SRR p.Asp257Asn Uncertain significance ★ ⚠ same type
SRR p.Asp258Gly Uncertain significance ★ ⚠ same type
SRR p.Gln296Glu Uncertain significance ★ ⚠ same type
SRR p.Gln296His Uncertain significance ★ ⚠ same type
SRR p.Glu304Gln Uncertain significance ★ ⚠ 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/srr-p-val174phe (accessed [today's date]).

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