Is SALL1 p.Ser86Phe (c.257C>T) pathogenic?

SALL1 p.Ser86Phe (c.257C>T) is classified Uncertain significance in SALL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-22). AlphaMissense: likely benign (0.1123); Ultra-rare (popmax 0.02%, amr); Associated with Townes-Brocks syndrome.

What condition is associated with SALL1 p.Ser86Phe (c.257C>T)?

SALL1 p.Ser86Phe (c.257C>T) is associated with Townes-Brocks syndrome (ClinVar).

How common is SALL1 p.Ser86Phe (c.257C>T) in the general population?

SALL1 p.Ser86Phe (c.257C>T) is ultra-rare (popmax 0.02%, amr) (gnomAD).

What do computational predictors say about SALL1 p.Ser86Phe (c.257C>T)?

AlphaMissense predicts likely benign (score 0.1123) — an in-silico prediction, not a clinical call.

SALL1 p.Ser86Phe

c.257C>T · VCV4803618

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1123 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Townes-Brocks syndrome

Computational evidence

Protein change
AlphaMissense	0.1123	likely benign
REVEL	0.091	moderately benign-leaning
SaProt	LLR -9.49	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 7.5	GERP 1.9, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 10 kb · p 0.25 · regional, not allelic
Overall
CADD	23.1	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 0.02% Admixed American · 12/59,990 alleles

Filtering AF 0.0115% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00898%

Overall 0.0057% 92/1,613,668 alleles · ultra-rare exomes 81/1,461,598 · genomes 11/152,070 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.02%	4,999
European (non-Finnish)	0.00636%	15,731
Remaining individualsnot grpmax-eligible	0.0032%	31,236
African / African-American	0.00267%	37,442
Finnishnot grpmax-eligible	0.00156%	63,992

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: SALL1
Protein: p.Ser86Phe
Coding: c.257C>T
MANE Select: NM_002968
Type: single nucleotide variant
Location: chr16:51141965 (GRCh38)
Gene constraint: LOEUF 0.228 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 49.54
Residue 86: the 'disordered' region

Full SALL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Townes-Brocks syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SALL1 p.Arg1054Ter Pathogenic/Likely pathogenic ★★ same condition
SALL1 p.Arg276Ter Pathogenic/Likely pathogenic ★★ same condition
SALL1 p.Arg786Ter Pathogenic ★★ same condition
SALL1 p.Gln272Ter Pathogenic ★★ same condition
SALL1 p.Gln291Ter Pathogenic/Likely pathogenic ★★ same condition
SALL1 p.Gln323Ter Pathogenic ★★ same condition
SALL1 p.Ala369Val Uncertain significance ★★ ⚠ same condition
SALL1 p.Ala637Val Uncertain significance ★★ ⚠ 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/sall1-p-ser86phe (accessed [today's date]).

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