Is SRRT p.Ala451Val (c.1352C>T) pathogenic?

SRRT p.Ala451Val (c.1352C>T) is classified Uncertain significance in SRRT (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-05). AlphaMissense: likely pathogenic (0.9674); Very rare (popmax 0.00237%, nfe).

How common is SRRT p.Ala451Val (c.1352C>T) in the general population?

SRRT p.Ala451Val (c.1352C>T) is very rare (popmax 0.00237%, nfe) (gnomAD).

What do computational predictors say about SRRT p.Ala451Val (c.1352C>T)?

AlphaMissense predicts likely pathogenic (score 0.9674) — an in-silico prediction, not a clinical call.

SRRT p.Ala451Val

c.1352C>T · rs888110002 · VCV3170241

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9674 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00237%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9674	likely pathogenic
REVEL	0.154	moderately benign-leaning
SaProt	LLR -9.71	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.7	GERP 1.5, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 2,248 bp · p 3.6e-06 · regional, not allelic
Overall
CADD	25.3	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 0.00237% European (non-Finnish) · 28/1,179,806 alleles

Filtering AF 0.00165% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00142%

Overall 0.00192% 31/1,613,548 alleles · very rare exomes 26/1,461,434 · genomes 5/152,114 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00237%	42,136
South Asian	0.0022%	45,518
African / African-American	0.00134%	74,870

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: SRRT
Protein: p.Ala451Val
Coding: c.1352C>T
MANE Select: NM_015908
dbSNP: rs888110002
Type: single nucleotide variant
Location: chr7:100885735 (GRCh38)
Gene constraint: LOEUF 0.404 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 66.61 · 6 PDB
Residue 451: a β-strand

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

Similar variants

SRRT c.1042-18C>G Benign ★★ same type
SRRT c.1042-7C>T Benign ★★ same type
SRRT c.2556-9A>T Benign ★★ same type
SRRT p.Arg518= Benign ★★ same type
SRRT p.Glu205= Benign ★★ same type
SRRT p.Leu157= Benign ★★ same type
SRRT p.Leu265= Benign ★★ same type
SRRT p.Ala190Val 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/srrt-p-ala451val (accessed [today's date]).

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