Is SUMF1 p.Cys13Phe (c.38G>T) pathogenic?

SUMF1 p.Cys13Phe (c.38G>T) is classified Uncertain significance in SUMF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-05). AlphaMissense: likely benign (0.0529); Ultra-rare (popmax 0.0121%, sas).

How common is SUMF1 p.Cys13Phe (c.38G>T) in the general population?

SUMF1 p.Cys13Phe (c.38G>T) is ultra-rare (popmax 0.0121%, sas) (gnomAD).

What do computational predictors say about SUMF1 p.Cys13Phe (c.38G>T)?

AlphaMissense predicts likely benign (score 0.0529) — an in-silico prediction, not a clinical call.

SUMF1 p.Cys13Phe

c.38G>T · VCV4961021

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0529 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0121%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0529	likely benign
REVEL	0.267	benign-leaning
SaProt	LLR -7.47	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.43	GERP -3.2
Regional constraint	o/e 1.18	unconstrained · MANE · 105 kb · p 0.0001 · regional, not allelic
Overall
CADD	0.248	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 0.0121% South Asian · 11/90,596 alleles

Filtering AF 0.0068% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00524%

Overall 0.00143% 23/1,611,502 alleles · ultra-rare exomes 18/1,459,286 · genomes 5/152,216 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0121%	8,236
Admixed American	0.00334%	29,914
East Asian	0.00223%	44,800
African / African-American	0.00134%	74,866
European (non-Finnish)	0.000678%	147,413

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.Cys13Phe
Coding: c.38G>T
MANE Select: NM_182760
Type: single nucleotide variant
Location: chr3:4467208 (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

Similar variants

SUMF1 p.Cys13Ter Pathogenic ★ same residue
SUMF1 p.Cys13Arg Uncertain significance ★ ⚠ same residue
SUMF1 p.Cys13Tyr Conflicting classifications of pathogenicity ★ ⚠ same residue
SUMF1 c.271-1G>C Likely pathogenic ★★ same type
SUMF1 c.445-1G>A Pathogenic/Likely pathogenic ★★ same type
SUMF1 c.445-2A>G Pathogenic/Likely pathogenic ★★ same type
SUMF1 c.520-1G>C Likely pathogenic ★★ same type
SUMF1 c.602+1G>A Pathogenic/Likely pathogenic ★★ 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/sumf1-p-cys13phe (accessed [today's date]).

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