Is SUMF1 p.Ser311Phe (c.932C>T) pathogenic?

SUMF1 p.Ser311Phe (c.932C>T) is classified Uncertain significance in SUMF1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-06-12). AlphaMissense: likely benign (0.2065); Ultra-rare (popmax 0.016%, afr); Associated with Inborn genetic diseases.

What condition is associated with SUMF1 p.Ser311Phe (c.932C>T)?

SUMF1 p.Ser311Phe (c.932C>T) is associated with Inborn genetic diseases, mucosulfatidosis (ClinVar).

How common is SUMF1 p.Ser311Phe (c.932C>T) in the general population?

SUMF1 p.Ser311Phe (c.932C>T) is ultra-rare (popmax 0.016%, afr) (gnomAD).

What do computational predictors say about SUMF1 p.Ser311Phe (c.932C>T)?

AlphaMissense predicts likely benign (score 0.2065) — an in-silico prediction, not a clinical call.

SUMF1 p.Ser311Phe

c.932C>T · rs552583949 · VCV902186

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.2065 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.016%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2065	likely benign
REVEL	0.642	indeterminate
SaProt	LLR -13.63	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 9.8	GERP 2.3, phastCons 1
Regional constraint	o/e 1.18	unconstrained · MANE · 105 kb · p 0.0001 · regional, not allelic
Overall
CADD	25.0	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 0.016% African / African-American · 12/75,048 alleles

Filtering AF 0.0092% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00721%

Overall 0.000805% 13/1,614,024 alleles · ultra-rare exomes 2/1,461,706 · genomes 11/152,318 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.016%	6,254
Remaining individualsnot grpmax-eligible	0.0016%	62,500

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: SUMF1
Protein: p.Ser311Phe
Coding: c.932C>T
MANE Select: NM_182760
dbSNP: rs552583949
Type: single nucleotide variant
Location: chr3:4410887 (GRCh38)
Gene constraint: LOEUF 1.254 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.39 · 21 PDB

Full SUMF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: mucosulfatidosis

Similar variants

SUMF1 c.271-1G>C Likely pathogenic ★★ same condition
SUMF1 c.445-1G>A Pathogenic/Likely pathogenic ★★ same condition
SUMF1 c.445-2A>G Pathogenic/Likely pathogenic ★★ same condition
SUMF1 c.520-1G>C Likely pathogenic ★★ same condition
SUMF1 c.602+1G>A Pathogenic/Likely pathogenic ★★ same condition
SUMF1 c.603-1G>C Pathogenic ★★ same condition
SUMF1 c.840+1G>A Likely pathogenic ★★ same condition
SUMF1 c.954+1G>T Likely pathogenic ★★ same condition

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/sumf1-p-ser311phe (accessed [today's date]).

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