Is SRRT p.Glu307Asp (c.921G>C) pathogenic?

SRRT p.Glu307Asp (c.921G>C) is classified Likely benign in SRRT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-22). AlphaMissense: likely benign (0.0613); Very rare (popmax 0.00556%, sas).

How common is SRRT p.Glu307Asp (c.921G>C) in the general population?

SRRT p.Glu307Asp (c.921G>C) is very rare (popmax 0.00556%, sas) (gnomAD).

What do computational predictors say about SRRT p.Glu307Asp (c.921G>C)?

AlphaMissense predicts likely benign (score 0.0613) — an in-silico prediction, not a clinical call.

SRRT p.Glu307Asp

c.921G>C · VCV4589745

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0613 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00556%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0613	likely benign
REVEL	0.028	moderately benign-leaning
SaProt	LLR -6.84	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.33	GERP -3.9, phastCons 0.073
Regional constraint	o/e 1.12	unconstrained · MANE · 784 bp · p 0.15 · regional, not allelic
Overall
CADD	7.637	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 0.00556% South Asian · 5/89,914 alleles

Filtering AF 0.00213% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00138%

Overall 0.00144% 22/1,524,198 alleles · very rare exomes 22/1,375,664 · genomes 0/148,534 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00556%	17,983
European (non-Finnish)	0.00151%	66,178

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.Glu307Asp
Coding: c.921G>C
MANE Select: NM_015908
Type: single nucleotide variant
Location: chr7:100884531 (GRCh38)
Gene constraint: LOEUF 0.404 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 66.61 · 6 PDB
Residue 307: the 'disordered' region

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-glu307asp (accessed [today's date]).

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