Is SRRT p.Gln515Arg (c.1544A>G) pathogenic?

SRRT p.Gln515Arg (c.1544A>G) is classified Uncertain significance in SRRT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-08). AlphaMissense: likely pathogenic (0.6281); Very rare (popmax 8.47e-05%, nfe).

How common is SRRT p.Gln515Arg (c.1544A>G) in the general population?

SRRT p.Gln515Arg (c.1544A>G) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about SRRT p.Gln515Arg (c.1544A>G)?

AlphaMissense predicts likely pathogenic (score 0.6281) — an in-silico prediction, not a clinical call.

SRRT p.Gln515Arg

c.1544A>G · VCV3801676

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6281 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6281	likely pathogenic
REVEL	0.179	moderately benign-leaning
SaProt	LLR -9.49	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.6, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 2,248 bp · p 3.6e-06 · regional, not allelic
Overall
CADD	26.0	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 8.47e-05% European (non-Finnish) · 1/1,180,018 alleles

Overall 6.2e-05% 1/1,613,890 alleles · very rare exomes 1/1,461,578 · genomes 0/152,312 · joint denominator

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.Gln515Arg
Coding: c.1544A>G
MANE Select: NM_015908
Type: single nucleotide variant
Location: chr7:100886332 (GRCh38)
Gene constraint: LOEUF 0.404 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 66.61 · 6 PDB
Residue 515: an α-helix

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

Similar variants

SRRT p.Gln515Glu Uncertain significance ★ ⚠ same residue
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

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-gln515arg (accessed [today's date]).

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