Is SRRT p.Asn508Ser (c.1523A>G) pathogenic?

SRRT p.Asn508Ser (c.1523A>G) is classified Uncertain significance in SRRT (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-27). AlphaMissense: likely benign (0.0631); Ultra-rare (popmax 0.0674%, nfe).

How common is SRRT p.Asn508Ser (c.1523A>G) in the general population?

SRRT p.Asn508Ser (c.1523A>G) is ultra-rare (popmax 0.0674%, nfe) (gnomAD).

What do computational predictors say about SRRT p.Asn508Ser (c.1523A>G)?

AlphaMissense predicts likely benign (score 0.0631) — an in-silico prediction, not a clinical call.

SRRT p.Asn508Ser

c.1523A>G · rs144966688 · VCV2218297

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0631 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0674%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.0631	likely benign
REVEL	0.391	indeterminate
SaProt	LLR -8.23	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
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	22.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0674% European (non-Finnish) · 795/1,180,012 alleles

Filtering AF 0.0635% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0619%

Overall 0.0526% 849/1,613,638 alleles · ultra-rare exomes 787/1,461,420 · genomes 62/152,218 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0674%	1,484
Remaining individualsnot grpmax-eligible	0.0304%	3,288
Admixed American	0.0233%	4,287
East Asian	0.0134%	7,479
African / African-American	0.012%	8,334
Finnishnot grpmax-eligible	0.00782%	12,791
South Asian	0.0011%	91,052

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.Asn508Ser
Coding: c.1523A>G
MANE Select: NM_015908
dbSNP: rs144966688
Type: single nucleotide variant
Location: chr7:100886311 (GRCh38)
Gene constraint: LOEUF 0.404 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 66.61 · 6 PDB

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

Similar variants

SRRT p.Asn508Ile 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-asn508ser (accessed [today's date]).

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