Is SMS p.Asp247Val (c.740A>T) pathogenic?

SMS p.Asp247Val (c.740A>T) is classified Uncertain significance in SMS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-24). AlphaMissense: likely benign (0.2032); Absent from gnomAD v4.1.

How common is SMS p.Asp247Val (c.740A>T) in the general population?

SMS p.Asp247Val (c.740A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SMS p.Asp247Val (c.740A>T)?

AlphaMissense predicts likely benign (score 0.2032) — an in-silico prediction, not a clinical call.

SMS p.Asp247Val

c.740A>T · VCV4687005

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2032 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2032	likely benign
REVEL	0.657	pathogenic-leaning
SaProt	LLR -11.81	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.2, phastCons 1
Regional constraint	o/e 0.34	constrained · MANE · 22 kb · p 3.7e-21 · regional, not allelic
Overall
CADD	26.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SMS
Protein: p.Asp247Val
Coding: c.740A>T
MANE Select: NM_004595
Type: single nucleotide variant
Location: chrX:21978956 (GRCh38)
Structure: AlphaFold pLDDT 95.09 · 2 PDB
Residue 247: the pabs domain

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

Similar variants

SMS p.Asp247Glu Uncertain significance ★ ⚠ same residue
SMS p.Arg234Ter Pathogenic/Likely pathogenic ★★ same type
SMS p.Gly203Asp Pathogenic ★★ same type
SMS p.Gly56Ser Pathogenic ★★ ⚠ same type
SMS p.Ile196Thr Likely pathogenic ★★ same type
SMS p.Pro112Leu Pathogenic/Likely pathogenic ★★ ⚠ same type
SMS c.1061+2T>C Uncertain significance ★★ same type
SMS c.505+3A>G 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/sms-p-asp247val (accessed [today's date]).

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