Is SELL p.Phe244Ser (c.731T>C) pathogenic?

SELL p.Phe244Ser (c.731T>C) is classified Uncertain significance in SELL (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-16). AlphaMissense: likely benign (0.0485); No allele count reported in gnomAD v4.1 (AN 1,580,332).

How common is SELL p.Phe244Ser (c.731T>C) in the general population?

SELL p.Phe244Ser (c.731T>C) is no allele count reported in gnomAD v4.1 (AN 1,580,332) (gnomAD).

What do computational predictors say about SELL p.Phe244Ser (c.731T>C)?

AlphaMissense predicts likely benign (score 0.0485) — an in-silico prediction, not a clinical call.

SELL p.Phe244Ser

c.731T>C · rs2525949456 · VCV3159672

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0485 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,580,332)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0485	likely benign
REVEL	0.116	moderately benign-leaning
SaProt	LLR -2.45	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.27	gain · loss 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 0.24	GERP -1.4
Regional constraint	o/e 1.03	unconstrained · MANE · 20 kb · p 0.58 · regional, not allelic
Overall
CADD	4.556	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

No allele count reported in gnomAD v4.1 (AN 1,580,332). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SELL
Protein: p.Phe244Ser
Coding: c.731T>C
MANE Select: NM_000655
dbSNP: rs2525949456
Type: single nucleotide variant
Location: chr1:169704603 (GRCh38)
Gene constraint: LOEUF 1.165 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.76 · 3 PDB
Residue 244: the sushi 1 domain

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

Similar variants

SELL p.Glu201Gln Benign ★★ same type
SELL p.Gly117= Benign ★★ same type
SELL c.-17A>G Uncertain significance ★ same type
SELL p.Ala158Asp Uncertain significance ★ ⚠ same type
SELL p.Ala277Val Uncertain significance ★ ⚠ same type
SELL p.Arg357Ile Uncertain significance ★ ⚠ same type
SELL p.Arg84Cys Uncertain significance ★ ⚠ same type
SELL p.Asn113Ser 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/sell-p-phe244ser (accessed [today's date]).

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