Is SRRT p.Ser88Arg (c.264C>G) pathogenic?

SRRT p.Ser88Arg (c.264C>G) is classified Uncertain significance in SRRT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-21). AlphaMissense: likely pathogenic (0.9195); Ultra-rare (popmax 0.01%, amr).

How common is SRRT p.Ser88Arg (c.264C>G) in the general population?

SRRT p.Ser88Arg (c.264C>G) is ultra-rare (popmax 0.01%, amr) (gnomAD).

What do computational predictors say about SRRT p.Ser88Arg (c.264C>G)?

AlphaMissense predicts likely pathogenic (score 0.9195) — an in-silico prediction, not a clinical call.

SRRT p.Ser88Arg

c.264C>G · VCV4589740

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9195 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.01%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9195	likely pathogenic
REVEL	0.183	benign-leaning
SaProt	LLR -4.88	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 0.62	GERP -2.1, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 8,778 bp · p 8.1e-06 · regional, not allelic
Overall
CADD	16.49	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 0.01% Admixed American · 6/59,996 alleles

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

Overall 0.000434% 7/1,613,928 alleles · ultra-rare exomes 6/1,461,770 · genomes 1/152,158 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.01%	9,999
European (non-Finnish)	8.47e-05%	1,180,032

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.Ser88Arg
Coding: c.264C>G
MANE Select: NM_015908
Type: single nucleotide variant
Location: chr7:100881671 (GRCh38)
Gene constraint: LOEUF 0.404 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 66.61 · 6 PDB
Residue 88: 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-ser88arg (accessed [today's date]).

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